Cardiotoxic drugs Herceptin and doxorubicin inhibit cardiac microvascular endothelial cell barrier formation resulting in increased drug permeability

Wilkinson, Emma L, Sidaway, James E and Cross, MJ ORCID: 0000-0002-5533-1232 (2016) Cardiotoxic drugs Herceptin and doxorubicin inhibit cardiac microvascular endothelial cell barrier formation resulting in increased drug permeability. Biology open, 5 (10). pp. 1362-1370.

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Official URL: https://bio.biologists.org/content/5/10/1362

Abstract

Cardiotoxicity induced by anti-cancer therapeutics is a severe and potentially fatal adverse reaction of the heart in response to certain drugs. Current in vitro approaches to assess cardiotoxicity have focused on analysing cardiomyocytes. More recently it has become apparent that non-cardiomyocyte cells of the heart can potentially contribute to cardiotoxicity. Herceptin and doxorubicin are known to induce cardiotoxicity in the clinic. The effect of these drugs on the endothelial tight junction barrier was tested by analysing tight junction formation and zona occludens-1 (ZO-1) levels, revealing that Herceptin and doxorubicin are able to induce barrier perturbment and decrease barrier function in human cardiac microvascular endothelial cells (HCMECs) leading to increased permeabilty. Herceptin treatment had no effect on the tight junction barrier function in human dermal and human brain microvascular endothelial cells. HCMECs showed detectable levels of HER2 compared with the other endothelial cells suggesting that Herceptin binding to HER2 in these cells may interfere with tight junction formation. Our data suggests that doxorubicin and Herceptin can affect tight junction formation in the cardiac microvasculature leading to increased permeability and adverse effects on the cardiac myocytes.

Item Type:	Article
Uncontrolled Keywords:	Cardiotoxicity, Cardiac permeability, Anthracycline, Herceptin, Endothelial
Depositing User:	Symplectic Admin
Date Deposited:	22 Aug 2016 15:07
Last Modified:	19 Jan 2023 07:32
DOI:	10.1242/bio.020362
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3003003